The cardiac action potential is generated by rapid ionic currents flowing across the membrane. The voltage clamp technique can directly measure the net membrane currents but cannot always directly determine the ionic species carrying the current or the time course of ionic accumulation. Using ion selective electrodes (ISE) in voltage clamped or normally beating canine Purkinje fibers and ventricular muscle, it is proposed to study the ionic components of the membrane currents as the changes in ionic activity on both side of the membrane. Furthermore, these changes in ionic activity may in themselves modulate membrane electrical behavior by altering passive or metabolically driven currents. It is specifically proposed to study with K ion - ISE the cycle dependent (beat to beat) fluctuations in extracellular K ion activity (aKo) and to determine the role of these fluctuations in controlling automaticity and action potential duration. Long term depletions of extracellular K ion following periods of overdrive have been attributed to sustained pumping activity due to the accumulation of intracellular Na ion. ISEs for K ion and Na ion will be used to study affects on automaticity and action potential duration (APD) during and after periods of overdrive when electrogenic currents associated with restoring ionic gradients may have a more significant effect than the ionic accumulations themselves. We will also study what role transmembrane Ca ions redistribution plays in automaticity by monitoring extracellular and Ca ions activity during overdrive and ionic, drug, and temperature interventions which affect automaticity. Information and techniques developed during the study of normal tissue will be used to reexamine the role of ionic accumulation in acute pathological states by examining slow conducting, glycoside toxic, and infarcted tissue.